Daiichi Sankyo has announced positive initial findings from the dose escalation phase of its Phase I trial of DS-9606, an antibody-drug conjugate (ADC) being investigated for the treatment of advanced solid tumors. The trial, developed in collaboration with the Tokyo University of Pharmacy and Life Sciences, is evaluating the safety, tolerability, and efficacy of DS-9606 in adult patients with Claudin-6 (CLDN6)-expressing advanced solid tumors in Europe and North America.
DS-9606 is designed using Daiichi Sankyo’s second ADC technology platform. It comprises a humanized CLDN6 monoclonal antibody linked to a modified pyrrolobenzodiazepine (PBD) payload. CLDN6 is a protein found in several tumor types, including endometrial, ovarian, and gastric cancers, germ cell tumors, and non-small cell lung cancer.
Promising Clinical Activity
The Phase I trial involved 53 heavily pretreated patients with various cancers, who had undergone a median of four prior therapies. Preliminary efficacy results showed four confirmed objective responses at doses greater than or equal to 0.072mg/kg. Notably, two responses were observed in patients with germ cell tumors, and one response each in patients with gastric/esophageal cancer and non-small cell lung cancer. Seven patients with germ cell tumors showed significant tumor marker reductions, with two maintaining treatment response for over six months. As of the data cutoff on 14 June 2024, 21 patients continue to receive DS-9606 treatment.
Safety and Tolerability Profile
The safety and tolerability of DS-9606 were assessed across doses ranging from 0.016 mg/kg to 0.225 mg/kg. No dose-limiting toxicities were observed, and no patients withdrew due to treatment-related adverse events. The most common treatment-emergent adverse events (TEAEs) included nausea, fatigue, and anemia, with Grade 3 or higher TEAEs occurring in 30.2% of patients.
Next Steps
The trial's next steps include determining the maximum tolerated dose and the recommended dose for expansion, followed by further evaluation in dose expansion cohorts. Daiichi Sankyo R&D global head Ken Takeshita stated that further clinical evaluation is warranted across different tumor types that are known to express CLDN6. He added, “We continue to apply our science and technology expertise to DS-9606, which has been developed from our second antibody-drug conjugate platform in order to create potentially new and innovative treatments for certain patients with cancer.”
